Psychiatric disorders are the leading source of disability worldwide (affecting 53% of the U.S. population). In addition to the individual suffering they entail, the disability associated with these disorders includes substantial consequences for family and health outcomes. This includes long term consequences for family formation and dissolution behaviors. Dissecting the relationship among community, family and psychiatric factors is complex because of the high potential for reciprocal causation. The result is a formidable challenge to understanding the role of psychiatric disorders in a wide range of adverse outcomes. The first step toward disentangling this complex relationship is to identify the role of causal factors that precede the formation of psychiatric disorders so that subsequent steps can estimate the mediating power of psychiatric disorders in long-term outcomes such as family formation and dissolution. In fact, this is such a high scientific priority for the NIH that they have already obtained special R56 funding on our behalf to conduct an initial phase of the project we now propose to complete. Here we propose to use the transformative new approach designed with the R56 support to significantly advance the study of both mental health and family. This project will capitalize on unprecedented opportunities to advance our understanding of the formation of psychiatric disorders. We propose to integrate: (1) a long-term community and family panel study with exceptional measurement of social environment (the Chitwan Valley Family Study ? CVFS); (2) a setting of unusually high exposures to risk factors (South Asia); and (3) recent advances in psychiatric genetics that have identified polygenic risk profiles contributing to psychiatric disorders. We focus on three psychiatric phenotypes that are common and have the best established relationship to family and social environment: major depressive disorder, post-traumatic stress disorder, and alcohol use disorder. Our specific aims are: (Aim 1) Create a unique scientific resource by collecting psychiatric phenotypes, demographic information and biospecimens from participants in the CVFS. The CVFS is an existing NICHD-funded study comprising 9,875 individuals from 2,700 households in various sub-population groups; (Aim 2) Conduct demographic/ epidemiologic analyses to identify key predictors of psychiatric disorder in a large population-based sample of South Asian families and communities in a controlled-comparison design; (Aim 3) Perform genomewide genotyping and analyses to examine the role of polygenic risk scores and genetic modifiers of environmental risk and resilience factors. The project will: (1) Extend both the demography of mental health and psychiatric genetic findings from the European Diaspora to South Asian populations; (2) Establish the role of community and gene-environment interactions in producing common psychiatric disorders most likely to shape long-term family outcomes; and (3) Create a transformative new scientific resource to learn the potential of psychiatric disorders to shape many different later life personal, family and health outcomes.